The Activity of TroVax® Versus Placebo in Relapsed Asymptomatic Ovarian Cancer (TRIOC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University College, London
Sponsor:
Collaborators:
Oxford BioMedica
Cancer Research UK
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01556841
First received: March 14, 2012
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

The purpose of this trial is to assess the effectiveness of TroVax® compared to placebo in extending the time to progression in patients with asymptomatic relapsed platinum resistant ovarian, fallopian tube or primary peritoneal cancer.The trial will also look at overall survival times and quality of life.


Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Biological: TroVax®
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Parallel Group Double-Blind Phase II Study to Assess the Activity of TroVax® (MVA-5T4) Versus Placebo in Patients With Relapsed Asymptomatic Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Progression [ Time Frame: At 25 weeks ] [ Designated as safety issue: No ]
    RECIST-defined progression


Secondary Outcome Measures:
  • Immune-related response criteria (irRC) [ Time Frame: 8 weeks post evidence of progression by RECIST 1.1 ] [ Designated as safety issue: No ]
    irRC will be used to identify any delayed response.Patients will remain on treatment until irRc has confirmed progression (in the absence of unacceptable toxicity or the need for urgent chemotherapy).

  • Progression-free survival [ Time Frame: Time from randomisation to clinical intervention or confirmed evidence of progression or death, assessed for up to 2 years ] [ Designated as safety issue: No ]
  • Time to clinical intervention [ Time Frame: Time from randomisation to clinical intervention or death, assessed for up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of clinical intervention [ Time Frame: At 25 weeks from randomisation ] [ Designated as safety issue: No ]
  • CA-125 doubling time [ Time Frame: Assessed at treatment visits for up to 2 years from randomisation. ] [ Designated as safety issue: No ]
    To investigate CA-125 doubling time as an independent prognostic factor.

  • Overall survival [ Time Frame: Time between randomisation and death assessed for up to 4 years ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: For up to 2 years following randomisation or until progression ] [ Designated as safety issue: No ]
    Patient reported outcome and health-related quality of life measured by standardised questionnaires (EORTC QLQ C-30, EORTC QLQ OV-28)


Estimated Enrollment: 100
Study Start Date: November 2013
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TroVax®
TroVax® consists of a highly attenuated VV (Modified Vaccinia Ankara, MVA) containing the human TAA 5T4 under regulatory control of a modified VV promoter, mH5.
Biological: TroVax®
Patients will be randomised to receive either TroVax® 1 x 10↑9 TCID50/mL in 1mL (experimental arm) or matched placebo (control arm) on a 1:1 basis. A single dose will be given by intramuscular injection during the following weeks: 2, 4, 7, 10, 13, 19, 25, 31, 37, 43 and 49. No further treatment will be given beyond week 49.Treatment will be stopped early if confirmed progression or unacceptable toxicity.
Placebo Comparator: Placebo Biological: Placebo
Matched placebo will be administered as above.

Detailed Description:

A significant number of patients with advanced ovarian cancer develop a "CA-125 relapse" without clinical symptoms and with a low volume disease on the CT scan. For this group of patients, no survival benefit has been demonstrated from early chemotherapy treatment and, on average, the time to start of chemotherapy is 5 months. Such patients could benefit from immunotherapy and the time to chemotherapy could potentially be prolonged. Multiple immunotherapy agents, such as anti-CA-125 antibodies and various vaccines, have been tested and, although there is plenty of evidence of immune response, this has not translated to a definitive clinical benefit and is not recommended in clinical practice

5T4 appears to be highly expressed in ovarian cancer and correlates with more advanced stage of disease and poorly differentiated tumours. TroVax®, the vaccine targeting 5T4, has an extensive record of safety and efficacy in humans and vaccination in patients with colorectal, renal, and prostate cancer resulted in immune cellular and humoral responses and signs of clinical benefit.

We propose a trial of TroVax® vaccination in patients with CA-125-relapsed asymptomatic ovarian cancer to assess the clinical efficacy and immunological responses as outlined in this protocol. To allow for capture of any delayed response to immunotherapy, patients who progress on RECIST 1.1 criteria and who do not experience toxicity from treatment will continue on the vaccine/placebo injection until repeat imaging at 8 weeks in order for immune-related response criteria (irRC) to be evaluated in addition to RECIST 1.1 criteria (these patients as a standard of care would not receive any other therapeutic intervention).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged ≥18 years with histologically or cytologically proven advanced (stage Ic - III) epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma
  • CA-125 > 2xULN at diagnosis
  • Completed cytoreductive surgery during the phase of first-line therapy including removal of bulky tumour masses and adequate surgical staging including a minimum of bilateral salpingo-oophorectomy, hysterectomy and omentectomy with ≤ 1cm residual disease
  • Completed first line platinum-based chemotherapy OR Completed second line chemotherapy of any type and first line platinum-based chemotherapy and have had complete response according to RECIST 1.1
  • Normal CA-125 following most recent chemotherapy
  • Have developed CA-125 relapse ≥6 months after most recent chemotherapy (see appendix 8) and are asymptomatic and do not require chemotherapy.
  • Subject is assumed to be clinically immunocompetent and is free of clinically apparent/active autoimmune disease (i.e. no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's disease, Hashimoto's thyroiditis, multiple sclerosis, and rheumatoid arthritis). Note: subjects with type I or type II diabetes mellitus can be included, as can subjects with controlled and rarely flaring rheumatoid disease (defined as recent flare within 6 months prior to randomisation)
  • Subject has adequate bone marrow function as defined by Haemoglobin ≥ 110 g/L, white cell count ≥ 3.0 x 109/L, Absolute Lymphocyte Count (ALC) ≥ 1.0 x 109/L, Absolute Neutrophil Count (ANC) ≥1.5 x 109/L , Platelet Count ≥ 100 x 109/L and <400 x 109/L, Monocytes <0.8 x 109/L
  • Adequate end-organ function: plasma creatinine ≤ 2x upper limit of normal, AST and/or ALT ≤ 2x upper limit of normal, Total Bilirubin ≤ 1.5x upper limit normal
  • ECOG performance status 0-1
  • Life expectancy ≥6 months and willing to be available to attend clinic visits for treatment and for follow-up
  • Ability to give written informed consent
  • Randomised within 28 days of CT scan and to be treated no later than 14 days from randomisation

Exclusion Criteria:

  • Carcino-sarcoma/MMMT
  • Cancer related symptoms, or disease recurrence requiring immediate treatment with chemotherapy
  • CT scan showing bulky disease requiring chemotherapy, as judged by the investigator
  • Major surgery/radiation therapy, immunotherapy or chemotherapy completed < 4 weeks prior to screening
  • Patients who are deemed as being immunosuppressed, receiving > 4 weeks parenteral or oral steroids, (nasal sprays and inhalers are permitted), or receiving immunosuppressive therapy following transplant
  • "Currently active" second malignancy, other than non-melanoma skin cancer. Subjects are not considered to have a "currently active" malignancy if they have completed therapy ≥3 years previously and have no known evidence of residual or recurrent disease
  • Concomitant use of supplements or complementary medicines/botanicals. The following exceptions are permitted at screening and during the course of the trial:

    • conventional multivitamin supplements
    • selenium
    • lycopene
    • soy supplements
    • Vitamin E
  • Evidence of significant clinical disorder or laboratory finding which in the opinion of the investigator makes it undesirable for the patient to participate in the trial. No participant should have a serious or uncontrolled intercurrent infection (including those positive for HIV, hepatitis B or C)
  • Psychiatric illnesses/social situations that limit compliance with protocol requirements
  • Allergy to egg proteins, neomycin or history of allergic response to vaccinia vaccines
  • Chronic (≥ 6 months) oral corticosteroid use except when prescribed as replacement therapy in the case of adrenal insufficiency. If previously used for ≥6 months then must have discontinued ≥3 months prior to randomisation.
  • Concurrent chemotherapy, immunotherapy, radiotherapy or investigational agents
  • Current or planned treatment with bevacizumab (wash out period of 4 weeks prior to start of treatment is permitted)
  • Prior exposure to TroVax®
  • Cerebral metastases (known from previous investigations or clinically detectable, surgically resected)
  • Patients on active treatment as part of another clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556841

Contacts
Contact: Laura Stylianou +44 2076799016 ctc.trioc@ucl.ac.uk
Contact: Yen Ngai +44 2076799747 ctc.trioc@ucl.ac.uk

Locations
United Kingdom
East & North Hertfordshire NHS Trust Not yet recruiting
Northwood, Middlesex, United Kingdom, HA6 2RN
Principal Investigator: Marcia Hall         
Leeds Teaching Hospitals NHS Trust Recruiting
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Principal Investigator: Geoff Hall         
The Clatterbridge Cancer Centre NHS Foundation Trust Recruiting
Bebington, Wirral, United Kingdom, CH63 4JY
Principal Investigator: Rosie Lord         
University Hospitals of Bristol NHS Foundation Trust Not yet recruiting
Bristol, United Kingdom, BS2 8ED
Principal Investigator: Axel Walther         
Velindre NHS Trust Not yet recruiting
Cardiff, United Kingdom, CF14 2TL
Principal Investigator: Louise Hanna         
Royal Surrey County Hospital NHS Foundation Trust Recruiting
Guildford, United Kingdom, GU2 7XX
Principal Investigator: Agnieszka Michael         
University College London Hospitals NHS Foundation Trust Not yet recruiting
London, United Kingdom, NW1 2PG
Principal Investigator: Rebecca Kristeleit         
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Andrew Clamp         
Nottingham University Hospitals NHS Trust Not yet recruiting
Nottingham, United Kingdom, NG5 1PB
Principal Investigator: Anjana Anand         
Oxford University Hospitals NHS Trust Recruiting
Oxford, United Kingdom, OX3 7LE
Principal Investigator: Shibani Nicum         
Plymouth Hospitals NHS Trust Recruiting
Plymouth, United Kingdom, PL6 8OH
Principal Investigator: Dennis Yiannakis         
Sponsors and Collaborators
University College, London
Oxford BioMedica
Cancer Research UK
Investigators
Principal Investigator: Agnieszka Michael, MBBS, PhD University of Surrey; Royal Surrey County Hospital NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01556841     History of Changes
Other Study ID Numbers: UCL/11/0119
Study First Received: March 14, 2012
Last Updated: April 11, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Gene Therapy Advisory Committee

Keywords provided by University College, London:
Randomised
Controlled
Trovax
MVA-5T4
5T4
Immunotherapy
Relapsed
Asymptomatic
Epithelial
Ovarian
Fallopian
Peritoneal

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014